Registration Dossier

Administrative data

Description of key information

Oral discriminating dose-level: 50 mg/kg (test substance, ITC 826, corrected for water content of 26.1%). Slight toxicity only in preliminary test at 200 mg/kg By analogy with ITC 826, THPC-urea-amine is considered as Harmful by oral route.
LD50 dermal (rat)/ITC 826: > 2000 mg AI/kg bw. By analogy with ITC 826, THPC-urea-amine is considered as not Harmful by dermal route.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
Value:
50 mg/kg bw
Quality of whole database:
No acute toxicity study by oral route was performed on the registered THPC-urea-amine. However, one study performed on ITC 826 (analogous) with good reliability was available (Kr. 2).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
No acute toxicity study by dermal route was performed on the registered THPC-urea-amine. However, one study performed on ITC 826 (analogous) with good reliability was available (Kr. 2).

Additional information

No acute toxicity studies have been carried out on the registered THPC-urea-amine. The studies submitted are for a closely related substance ITC 826. Read-across is considered justified since the only differences between ITC 826 and the current product are in amine carbon chain length (C16 -18for ITC 826 and C14for the registered THPC-urea-amine).

 

1- Acute oral toxicity:

One study was available with reliability 2 according to Klimisch rating.

One study report (Lees, 1996) is available and has been chosen as key study for this endpoint. This study was conducted according to a protocol similar to OECD guideline 420 and in compliance with GLP. The test substance ITC 826 Concentrate. In a preliminary test in which a single Wistar-derived rat was administered 50, 200 or 500 mg/kg (corrected for water content of 26.1%) once by gavage and observed for 14 days. No mortalities and slight toxicity were observed at 200 mg/kg. The female dosed at 500 mg/kg was found dead in day 2.

A single dose of 50 mg/kg was selected for the main study in 5 male and 5 female rats. There were no signs of evident toxicity and 50 mg/kg was considered the discriminating dose-level. According to the current OECD guideline 420, since there were no treatment-related deaths and no evident toxicity at 50 mg/kg, a further group of 5 rats should have been tested at 300 mg/kg to distinguish between classification in Acute category 3 or 4. However, since only slight clinical signs were observed in the preliminary study at 200 mg/kg, it is considered that this deviation does not prevent a decision on classification being made.

By analogy with ITC 826, THPC-urea-amine is considered as harmful if swallowed according to EU criteria.

 

2- Acute dermal toxicity:

One study is available for this endpoint and considered as the key study (Lees, 1996). This study was conducted according to EU method B.3 and in compliance with GLP (Rel. 2).The test substance was ITC 826 Concentrate. Groups of Wistar-derived rats (5/sex/group) were dermally exposed to the test substance at a limit dose level of 2000 mg (test material corrected for water content of 26.1%) and observed for 14 days. There were no deaths or signs of systemic toxicity. All animals showed expected gain in body weight. Slight to moderate local irritation was observed in all the animals. Signs of necrosis were observed in two males and in one female. There was clear evidence of recovery and repair in these animals at the end of the observation period.

 

The dermal LD50 combined of THPC-urea-amine was greater than 2000 mg/kg bw (test substance corrected for water content), with neither deaths nor systemic effects during the study period.

By analogy with ITC 826, THPC-urea-amine is considered as not harmful by dermal route according to EU criteria.

 

3- Acute inhalation toxicity:

No data was available.

 Justification for selection of acute toxicity – oral endpoint

Only one acute study was available. 

Justification for selection of acute toxicity – inhalation endpoint 

waiving based on the corrosive properties of the submitted substance (category 1B; H314). 

Justification for selection of acute toxicity – dermal endpoint 

Only one acute study was available.


Justification for classification or non-classification

1- Acute oral toxicity:

Based on a discriminating dose-level of 50 mg/kg (test substance, ITC 826, corrected for water content of 26.1%), with only slight toxicity at 200 mg/kg, from a Rel. 2 study according to OECD 420, THPC-urea-amine is classified in category 4, H302 according to theCLPregulation (1272/2008) and as harmful if swallowed (Xn; R22) according to the Directive 67/548/EEC.

 

2- Acute dermal toxicity:

As the dermal LD50 of ITC 826 was found to be greater than 2000 mg/kg (test substance corrected for water content of 26.1%) with neither deaths nor systemic effects observed during the study period, THPC -urea-amine is not classified according to the EU legislation (Directive 67/548/EEC and CLPregulation (1272/2008)).

3- Acute inhalation toxicity:

No classification is possible due to lack of data.